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Gamma-hydroxybutryic acid, or GHB, is an abused xenobiotic and a neurotransmitter and neuromodulator that is produced in the brain. It has also been synthesized and used and abused in this form. It has been used experimentally to treat absence seizures in animals,63 as an adjunct to general anesthesia, as a sleep agent, as an anabolic nutritional supplement, and to treat alcohol dependence and alcohol withdrawal.30,45,51,73 It is classified as a Schedule I drug due to its popularity as a drug of abuse and its association with drug facilitated sexual assault, and also as a Schedule III drug for the treatment of narcolepsy.22 Two precursors of GHB, γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD)64 have many industrial uses but are also used as recreational drugs and as drugs to achieve chemical submission (as "date rape" drugs). These two precursors exert their effects through conversion to GHB.8,52 Numerous other analogs of GHB have industrial and commercial uses (see Table 80–1) and may result in GHB intoxication.

GHB was discovered in 1960 while searching for an analog for γ-aminobutyric acid (GABA).33 Due to its CNS depressive and amnestic properties, GHB was used initially as an anesthetic adjunct, especially in Europe but never gained favor in the United States for this indication. During the 1970s, an FDA-investigational new drug protocol was submitted to test the use of GHB as a treatment for sleep disturbances. In the 1980s and 1990s, body builders popularized GHB as an anabolic dietary supplement due to its release of growth hormone. Its euphoric effects were recognized at this time, and it rapidly gained favor as a "club drug." Because it can cause coma and profound amnesia, GHB has been used in drug-facilitated sexual assault, and in 1990 the FDA banned all use of nonprescription GHB due to this concern.61

Following the FDA ban, the analogs GBL and 1,4-BD were quickly substituted for GHB in dietary supplements. After the Samantha Reid and Hillory J. Farias Date-Rape Prevention Act of 1999 was passed in 2000 the DEA classified GHB and its analogs as Schedule I substances claiming that GHB was a hazard to public safety.19,61 Also in 2000, a new drug application was submitted to the FDA for GHB—under the generic name sodium oxybate and the trade name Xyrem®...